RT Journal Article SR Electronic T1 De novo DNA methyltransferase activity in colorectal cancer is directed towards H3K36me3 marked CpG islands JF bioRxiv FD Cold Spring Harbor Laboratory SP 676346 DO 10.1101/676346 A1 Roza H. Ali Masalmeh A1 Cristina Rubio-Ramon A1 Francesca Taglini A1 Jonathan Higham A1 Hazel Davidson-Smith A1 Richard Clark A1 Jimi Wills A1 Andrew J. Finch A1 Lee Murphy A1 Duncan Sproul YR 2019 UL http://biorxiv.org/content/early/2019/06/21/676346.abstract AB The aberrant gain of DNA methylation at CpG islands (CGIs) is frequently observed in colorectal tumours and may silence the expression of tumour suppressors such as MLH1. Current models propose that these CGIs are targeted by de novo DNA methyltransferases (DNMTs) in a sequence-specific manner but this has not been tested. Using ectopically integrated CGIs, we find that aberrantly methylated CGIs are subject to low levels of de novo DNMT activity in colorectal cancer cells. By delineating DNMT targets, we find that instead de novo DNMT activity is targeted primarily to CGIs marked by the histone modification H3K36me3, a mark associated with transcriptional elongation. These H3K36me3 marked CGIs are heavily methylated in colorectal tumours and the normal colon suggesting that de novo DNMT activity at CGIs in colorectal cancer is focused on similar targets to normal tissues and not greatly remodelled by tumourigenesis.